Trypanosoma brucei: Immunogenicity of the variant surface coat glycoprotein of virulent and avirulent subspecies

Abstract

Comparative analyses were made to define the immunogenic role in mice of the variant surface coat glycoprotein (VSG) of African trypanosomes. Less than 10 μg of the glycoprotein fixed to trypanosomes or covalently linked to sheep erythrocytes were 100 times more immunogenic than soluble VSG. Therefore, although VSG is present on the parasites and in the blood of infected hosts, the cell-bound form most likely elicits immunity. Intravenous administration of soluble or cell-bound VSG was a better route of immunization than the subcutaneous route. Therefore, although parasites grow at the site of infection, in tissue spaces, and in the blood, control of blood parasitemia is best developed if the antigen is introduced to the vascular bed. Full protection against homologous challenge occurred by 4 days and was maintained through 30 days. Trypanosome-agglutinating antibody titers could be measured at 3 days, peaked at 5 days, and remained high through 14 days after immunization. Therefore, mice immunized with an optimal dosage of VSG, 2 days before challenge, should have had ample time to elicit a protective response. Most of these mice, however, developed patent infections, and one-third died during the first peak of parasitemia at about the same time as untreated control mice. This indicates that active infection inhibits the early phases of induction of immunity. Mice, suboptimally immunized against and challenged with an avirulent isolate of Trypanosoma brucei gambiense, survived at higher rates than mice immunized and challenged with a virulent clone of T. b. rhodesiense. Cell-fixed and soluble VSG from both parasites elicited similar agglutinating-antibody titers, indicating that the two trypanosomes were equally antigenic. Results from neutralization tests, however, revealed that, per unit of immune mouse serum, 400 times more T. b. gambiense became noninfective than T. b. rhodesiense. Apparently, virulence is related to relative sensitivity of the trypanosomes to immunological assault.